Impact of both socioeconomic level and occupation on antibody prevalence to SARS-CoV-2 in an Egyptian cohort: The first episode.

We studied the impact of socioeconomic level on the anti-SARS-CoV-2-antibodies prevalence in an Egyptian cohort. The low socioeconomic standard group (LSS) included 51 humans, 30 females (F) and 21 males (M). The high socioeconomic standard group (HSS) included 55 subjects, 24 F and 31 M. Of the 30 LSSF, 6 were immunoglobulin M (IgM), 21 immunoglobulin G (IgG), and 6 double positive. Of the 21 LSSM, 5 were IgM, 12 IgG, and 5 double positive. Of the 24 HSSF, 6 were IgM, 11 IgG, and 5 double positive. Of the 31 HSSM, 6 were IgM, 14 IgG, and 4 double positive. Of the 51 LSS humans, 26 were symptomatic (S) and 25 asymptomatic (AS). Of the 26 S, 20 were IgG and 8 IgM/IgG double positive. Of the 25 AS, 13 were IgG and 3 IgM/IgG double positive. Of the 55 HSS humans, 38 were S and 17 AS. Of the 38S, 24 were IgG and 11 IgM positive of whom, 9 were double positive. Of the 17 AS, one was IgG and one IgM positive. The IgM prevalence was higher among the HSS humans. The IgG prevalence was significantly higher among the LSS humans. In the two different socioeconomic standards, the prevalence of either IgM or IgG was higher among F. An inverse correlation was observed between age and the anti-SARS-CoV-2-antibodies prevalence except for LSSF-IgG and LSSM-IgM. In conclusion, socioeconomic standard, gender, and age impact humoral responses to SARS-CoV-2 with a clear heterogeneity in individualized responses to the infection in terms of symptoms.

Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation.

4-(2-(4-Halophenyl)hydrazinyl)-6-phenylpyridazin-3(2H)-ones 1a,b were prepared and treated with phosphorus oxychloride, phosphorus pentasulphide and ethyl chloroformate to give the corresponding chloropyridazine, pyridazinethione, oxazolopyridazine derivatives 2-4, respectively. Compound 2 reacted with hydrazine hydrate to afford hydrazinylpyridazine 7. The reaction of 4-(2-(4-chlorophenyl)hydrazinyl)-3-hydrazinyl-6-phenylpyridazine (7) with acetic anhydride, p-chlorobenzaldehyde and carbon disulphide gave the corresponding pyridazinotriazine derivatives 8-10. On the other hand, 5-(4-chlorophenylamino)-7-(3,5-dimethoxybenzylidene)-3-phenyl-5H-pyridazino[3,4-b][1,4]thiazin-6(7H)-one (11) was prepared directly from the reaction of compound 3 with chloroacetic acid in presence of p-chlorobenzaldehyde. Compound 11 reacted with nitrogen nucleophiles (hydroxylamine hydrochloride, hydrazine hydrate) and active methylene group-containing reagents (malononitrile, ethyl cyanoacetate) to afford the corresponding fused compounds 12-15, respectively. Pharmacological screening for antiviral activity against hepatitis A virus (HAV) was performed for the new compounds. 4-(4-Chlorophenylamino)-6-phenyl-1,2-dihydropyridazino[4,3-e][1,2,4]triazine-3(4H)-thione (10) showed the highest effect against HAV.

Analysis of the SARS-CoV-2 nsp12 P323L/A529V mutations: coeffect in the transiently peaking lineage C.36.3 on protein structure and response to treatment in Egyptian records.

SARS-CoV-2 nsp12, the RNA-dependent RNA-polymerase plays a crucial role in virus replication. Monitoring the effect of its emerging mutants on viral replication and response to antiviral drugs is important. Nsp12 of two Egyptian isolates circulating in 2020 and 2021 were sequenced. Both isolates included P323L, one included the A529V. Tracking A529V mutant frequency, it relates to the transience peaked C.36.3 variant and its parent C.36, both peaked worldwide on February-August 2021, enlisted as high transmissible variants under investigation (VUI) on May 2021. Both Mutants were reported to originate from Egypt and showed an abrupt low frequency upon screening, we analyzed all 1104 nsp12 Egyptian sequences. A529V mutation was in 36 records with an abrupt low frequency on June 2021. As its possible reappearance might obligate actions for a candidate VUI, we analyzed the predicted co-effect of P323L and A529V mutations on protein stability and dynamics through protein structure simulations. Three available structures for drug-nsp12 interaction were used representing remdesivir, suramin and favipiravir drugs. Remdesivir and suramin showed an increase in structure stability and considerable change in flexibility while favipiravir showed an extreme interaction. Results predict a favored efficiency of the drugs except for favipiravir in case of the reported mutations.

Proinflammatory Cytokine Profiles in Both Mild Symptomatic and Asymptomatic SARS-CoV-2-Infected Egyptian Individuals and a Proposed Relationship to Post-COVID-19 Sequela.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with proinflammatory cytokine release as mediators of host antiviral response to the infection. Cytokine persistent elevation leads to post-Coronavirus disease-2019 (COVID-19) post-COVID-19 sequela (PCS) reported in about 60% of patients affecting individual's normal life after recovery. This study evaluates relationship of cytokines and chemokines pattern during and postinfection to PCS events. Serum samples collected from 82 individuals with symptomatic, asymptomatic, or no SARS-CoV-2 infection were classified as recently or formerly infected groups according to levels of anti-2019nCoV Immunoglobulin G/Immunoglobulin M. Levels of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, interferon alpha (IFN-α), tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein-1 were assessed via ELISA for each individual. All asymptomatic groups showed nonsignificant differences in cytokines' levels than control group. Significant elevation of IFN-α, TNF-α, and GM-CSF levels were observed in recent symptomatic, while IFN-α and TNF-α levels were significant in former symptomatic groups. We observed an association between fever with IL-1α and IFN-α levels, fatigue with TNF-α and GM-CSF, dyspnea with IFN-α, TNF-α, and GM-CSF, and chest-wheezing with GM-CSF. Individuals were surveyed 12 months postsampling for PCS events. Among 35 responders to survey, 8 (22.8%) reported PCS events, 6 of which were females. Upon studying PCS events, IL-8, IFN-α, TNF-α, and GM-CSF levels showed significant elevation in active infection, that was not seen in a resolved state of infection. Cytokines patterns suggest that either a persistent elevation in levels or damage caused during infection contributes to PCS. Although with the limited sample size, our study emphasizes the importance to conduct medical approaches targeting the associated cytokines to improve the PCS symptoms.

TLR3\TLR7 as Differentially Expressed Markers Among Viral, Nonviral, and Autoimmune Diseases in Egyptian Patients.

Toll-like receptors (TLRs) represent the immune link between the innate and the adaptive immune signals against various pathogens. This study aimed to evaluate the TLRs3 and 7 as immune-markers in differentiating between hepatitis C virus (HCV)-infected and -uninfected patients. Also, the use of the TLR3 and TLR7 as immune markers was compared with the prevalent bio and immune markers for autoimmune diseases in HCV-infected or -uninfected patients. The levels of GPT, GOT, B cell activated factors, tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-10 were measured in plasma, while the levels of TLR3 and TLR7 were quantified in lysates of peripheral blood mononuclear cells from healthy donors, HCV-infected patients, nonalcoholic fatty liver (NAFL) patients without autoimmune diseases and with autoimmune diseases (HCV-infected patients with autoimmune diseases [HCV+auto], nonalcoholic fatty liver patients with autoimmune diseases [NAFL+auto]), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) patients. The relative expression of TLR3, TLR7, TNF, and IL-10 in cell lysates was assessed against glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by quantitative real time-polymerase chain reaction (qRT-PCR). Results showed that TLRs 3 and 7 levels were significantly higher in SLE, RA, HCV, HCV+auto, and the NAFL patients compared to the normal control. The cell lysates from SLE patients expressed TLR3 at relatively significantly higher mRNA levels compared to normal subjects or other patient groups. The NAFL+auto patients expressed TLR7 at relatively significantly high mRNA levels compared to normal subjects or other patients. The RA patients expressed TLR7 at relatively significantly higher mRNA levels when compared to HCV, HCV+auto, and NAFL+auto patients. Conclusions: At the protein level, TLR7 can differentiate between HCV and NAFL patients. In addition, both TLRs3 and 7 can serve as potent markers in differentiating between NAFL and NAFL+auto.